Infection of animals via natural contagion demonstrates that animals are more susceptible to Sendai virus derived from syngeneic animals than to virus derived from allogeneic animals. Priming with allogeneic spleen cells improves survival of animals which are challenged with virus derived from that allogeneic strain. Experiments employing direct intranasal viral challenge confirm these findings. These data suggest that susceptibility to Sendai virus may be influenced by recognition of host derived histocompatibility antigens on the virion.